ZOLEDRONIC ACID ADMINISTRATION ENHANCES FRACTURE HEALING IN THE OSTEOPOROTIC FRACTURES IN OVARIECTOMIZED RABBITS

Gokhan Cansabuncu, Namik Sahin, Yavuz Akalin, Nazan Cevik, Guven Ozkaya

Abstract


Objectives: To evaluate the radiological, histological and mechanical effects on osteoporotic fracture healing of single-dose zoledronic acid (ZA) applied to an animal model with an experimentally created osteoporotic bone fracture.

Methods: A total of 14 adult, female New Zealand rabbits, aged 5-6 months were used in the study. Bone mineral density (BMD) values were calculated from bone densitometry measurements and recorded. Bilateral ovariectomy was then applied to all the rabbits. At 10 weeks after ovariectomy, bone densitometry was again performed on all the animals and the BMD values were compared. Osteoporosis was accepted as having developed in animals determined with a reduction of 28% in BMD values. After the placement of a K-wire intramedullarly in the femurs of the rabbits, a closed fracture was created with the standard method. The animals were then randomly separated into 2 groups as the zoledronic acid group (ZAG) and the control group (CG). An infusion of 0.1mg/kg ZA was administered to the ZAG animals from the ear vein. With visualisation of bone union rabbits were sacrificed by decapitation. Radiological, mechanical and histological assesments were then applied.

Results: In the histological evaluation, the mean histological score was determined as 5.00 in the ZAG and 3.00 in the CG. The difference between the groups was found to be statistically significant (p<0.001). In the radiological evaluation, the mean score was 7.00 in the ZAG and 6.25 in the CG. Even though higher points were obtained by the ZAG in the inter-observer evaluations, the difference between the groups was not statistically significant (p=0.073). In the mechanical evaluation, the elasticity collapse in negative proportion to rigidity was measured as 2.91 mm in the ZAG and 3.96mm in the CG (p=0.686). The rigidity data of the ZAG were higher in the mechanical tests but the difference between the groups was not statistically significant (p=0.086).

Conclusion: As the results of the study showed that the ZAG had higher values than those of the CG in all the histological, mechanical and radiological evaluations, the application of a single dose of ZA can be considered to increase the healing of osteoporotic fractures.


Keywords


Bone healing; Osteoporosis; Ovariectomy; Zoledronic acid; Animal Model

Full Text:

PDF

References


Li EC, Davis LE. Zoledronic acid: A new parenteral bisphosphonate. Clin Ther. 2003; 25(11): 2669-708.

McDonald M, Dulai S, Godfrey C, Amanat N, Sztynda T, Little DG. Bolus or weekly zoledronic acid administration does not delay endochondral fracture repair but weekly dosing enhances delays in hard callus remodeling. Bone. 2008; 43(4): 653-62.

Matos MA, Arao FP, Paix FB. The effect of zoledronate on bone remodeling during the healing process. Acta Cirurgica Brasileira. 2007; 22(2): 115-9.

Amanat N, McDonald M, Godfrey C, Bilston L, Little D. Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Minel Res. 2007; 22(6): 867-76.

Sambrook P, Cooper C. Osteoporosis. Lancet. 2006; 367(9527): 2010-18.

Giannoudis P, Tzioupis C, Almalki T, Buckley R. Fracture healing in osteoporotic fractures: is it really different? A basic science perspective. Injury. 2007; 38(suppl 1): S90-9.

Bonnarens F, Einhorn TA. Production of a standard closed fracture in laboratory animal bone. J Orthop Res. 1984; 2(1): 97-101.

An YH, Friedman RJ, Draughn RA. Animal models for bone Fracture or osteotomy. In An YH, Friedman RJ. Animal Models in Orthopaedic research. PA ; CRC press 1999; 208.

Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res. 1991; 9(3): 383-90.

Madsen JE, Berg-larsen T, Kirkeby OJ, Falch JA, Nordsletten L. No adverse effects of clodronate on fracture healing in rats. Acta Orthop Scand. 1998; 69(5): 532-6.

Koivukangas A, Tuukkanen J, Kippo K, Jämsä T, Hannuniemi R, Pasanen I et al. Long-term administration of clodronate does not prevent fracture healing in rats. Clin Orthop Relat Res. 2003; 408: 268-78.

Li J, Mori S, Kaji Y, Kawanishi J, Akiyama T, Norimatsu H. Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats. J Bone Min Res. 2000; 15(10): 2042-51.

Sevil F, Kara ME. The effects of ovariectomy on bone mineral density, geometrical, and biomechanical characteristics in the rabbit femur. Vet Comp Orthop Traum. 2010; 23(1): 31-6.

Castada S, Calvo E, Largo R, Gonzez-Gonzez R, de la Piedra C, Diaz-Curiel M et al. Characterization of a new experimental model of osteoporosis in rabbits. J Bone Miner Metab. 2008; 26(1), 53-9.

Baofeng L, Zhi Y, Bei C, Guolin M, Qingshui Y, Jian L. Characterization of a rabbit osteoporosis model induced by ovariectomy and glucocorticoid. Acta Orthop. 2010; 81(3): 396-401.

Arslan H, Ketani A, Gezici A, Kapukaya A, Necmioglu S, Kesemenli C et al. The effects of osteoporosis on distraction osteogenesis: an experimental study in an ovariectomised rabbit model. Acta Orthop Belq . 200 3; 69(1): 67-73.

Tarvainen R, Olkkonen H, Nevalainen T, Hyven P, Arnala I, Alhava E. Effect of clodronate on fracture healing in denervated rats. Bone. 1994;15(6): 701-5.

Hao Y, Wang X, Wang L, Lu Y, Mao Z, Ge S et al. Zoledronic acid suppresses callus remodeling but enhances callus strength in an osteoporotic rat model of fracture healing. Bone. 2015; 81: 702-11.

Peter CP, Cook WO, Nunamaker DM, Provost MT, Seedor JG, Rodan GA. Effect of alendronate on fracture healing and bone remodeling in dogs. J Orthop Res 1996; 14(1): 74-9.




DOI: http://dx.doi.org/10.24125/sanamed.v14i1.288

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.